Programmable DNA ‘smart glue’ could speed 3D-printed organ research

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Making synthetic organs is no longer just the stuff of science fiction, but in many cases the research is still quite primitive. Organs like bladders and ears are fairly homogenous — just one or two basic cell types laid out in a fairly simple physical configuration — and growing such a structure is fairly achievable by the standards of modern science. What’s more difficult is growing something like a liver, which incorporates many different cell types in a highly interdependent way, and arranged in a complex, highly detailed configuration. You need to grow a liver not just with the precise right sequence of hormones and growth factors, but on the correct physical substrate to allow a working final organ. A new breakthrough using DNA to provide the “glue” in a 3D printing material could help provide those substrates, printed to the right shape and genetically tailored to promote just the sort of growth we need.

The innovation here is in coating the a fluid-like collection of micro-beads with fragments of DNA. The researchers have designed DNA sequences that are complementary to one another, then fragmented (broken up) and bound to the micro-beads; when you mix together two types of beads coated with complementary sequences, they anneal to one another and stiffen into a gel-like colloidal structure. Outfit a 3D printer to mix them together and squirt the still-annealing gel out, and you’ve got yourself a DNA-based 3D printer.

The utility of this might not be immediately apparent, and indeed to the naked eye it looks pretty useless. Where DNA:DNA interactions can have an advantage over the regular chemical bonds between molecules in a conventional printing plastic is that DNA can be programmed. By specifically tailoring the sequences they attach to the beads, the researchers can program the final gel structure at the micro level — and as stated, one of the biggest challenges for organ growth is to give them the right small-scale environment for growth. With the ability to bead-bead interactions to form specifically the 3D structure we need, it might be possible to 3D print precisely the right environment for a particular combination of tissues.

Additionally, DNA-coated beads could carry and physically orient molecules that do more than simple annealing; there’s nothing to say these beads could also be coated with an increasing density of a particular growth factor, leading a desired cell type to grow along the concentration gradient in a very specific way. And since DNA is quite fragile, the conditions that allow DNA-coated beads to exist are also livable to most types of cells, so the bead-gels could be laced with our cell types of interest.

In principle, this could lead to a future in which your outgoing organ is scanned, probably by MRI, and this scan is used to design the large-scale structures of the printing scaffold. The small-scale structure of the tissues will be roughly the same for all livers, and the combination of beads necessary to create it sits ready in the laboratory freezer. Feed the scan and the right beads to the printer, along with samples of liver cells to be deposited in the gel as it is laid down. Print. Wait. Surgery.

Of course, there are potential problems. For one, as mentioned, DNA is very fragile. The DNA interactions might not be able to last long enough to grow a whole liver, though the growing field of synthetic nucleic acids (so-called XNAs) could address this by creating a much more stable version of DNA with all the sequence advantages intact. Or, slow-forming chemical bonds could lock a configuration in place once the DNA had figured it out transiently.

The ability to read, construct, and manipulate DNA has come a long way in the past few years, and it’s leading to an explosion of applications. Researchers are using DNAs, RNAs, and now XNAs to build everything from (metaphorical) robots that pull drug molecules through your bloodstream, to synthetic genomes for all-new organisms — to DNA-coated beads that let us 3D print in the medium of life.

It’s no accident that all life is based on a nucleic acid at its heart; the incredible, algorithmic complexity that can come from such reliable chemical rules is unmatched, even by modern computing architecture. As researchers tailor XNAs to better offset DNA’s less helpful attributes, the possibilities will continue to grow. Evolution was able to use nucleic acids to create literally all of the variety we see in life around us today, with no will or intention.